Science Pool

Regulated ADMET Services Fact Sheet

Posted by Evotec on Mar 2, 2022 1:34:27 PM

Download this fact sheet to learn more about our regulatory ADMET services including:

  • Full support of development projects to fulfill and anticipate regulatory requirements
  • Accelerated development process with a full vision through all drug development phases up to filing
  • Dynamic team of expert scientists capable of handling projects of any complexity in regulated environment
  • Full integration with in-house bioanalytical and safety assessment groups
  • Tailored studies and programs based on specific client needs

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Tags: Fact Sheets, ADME/DMPK, IND Enabling Studies/Preclinical Development, Toxicology & Safety

Safety Assessment Fact Sheet

Posted by Evotec on Feb 10, 2022 10:01:32 AM

Learn more about our safety assessment services including:

  • Toxicology core capabilities
  • Safety pharmacology (GLP) studies
  • Genetic toxicology (GLP) studies
  • Additional capabilities such as bioanalytical method development and GLP validation, DMPK, immunoassays, immunogenicity testing, immunotoxicology assays

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Tags: INDiGO, Fact Sheets, ADME/DMPK, IND Enabling Studies/Preclinical Development, Toxicology & Safety

PK Prediction for Early Drug Discovery- Simon Thomas, Cyprotex

Posted by Evotec on Jan 31, 2022 1:17:56 PM

Learn about exciting new developments in pharmacokinetic prediction, and how to transform your use of ADME data.

 


About the Webinar

 

Whilst early in vitro screening for absorption, distribution metabolism and elimination (ADME) properties has significantly transformed early drug screening in many companies, the corresponding ability to quickly, and reliably, predict pharmacokinetics (PK) from these data has lagged behind. In vivo human prediction still largely relies on scaling from animal in vivo PK data, precluding its use for mass PK screening in early discovery.

In this webinar our expert, Simon Thomas, outlines Cyprotex's most recent work in the prediction of human PK from early ADME data. Combining ADME data with physicochemical and structural information within a novel physiologically based pharmacokinetic (PBPK) model, we have developed a service that returns a comprehensive array of reliable PK data and metrics: summary PK parameters and plasma concentrations are predicted for oral, intravenous bolus and intravenous infusion administration, whether single- or repeat-dose regimes. Generation of these predictions greatly enhances the value of the ADME data, and facilitates multiple options for directing compound progression: use of the predicted PK parameters enables compounds with desirable properties to be identified, whilst reliable plasma concentration prediction enables the implementation of pharmacokinetic/pharmacodynamic (PK/PD) modelling for early assessment of in vivo potential. High throughput and rapid turnaround maximally facilitate the make-test-analyse process.

 


About the Speaker

 

Simon Thomas resize bw

Simon Thomas PhD

Head of Modelling and Simulation | Cyprotex

Dr Simon Thomas is the Head of Modelling and Simulation at Cyprotex where he is responsible for the development of mathematical models for predicting ADME properties, pharmacokinetics, toxicity and clinical efficacy. Simon studied chemistry at the University of Oxford, as a final year student writing his first computer models, on the emission of electrons via the photoelectric effect. He obtained his Ph.D. and carried out post-doctoral work in the nascent field of systems biology at Oxford Brookes University, modelling the regulation of biochemical pathways in plants and animals, particularly with respect to pathways of energy metabolism. He joined Cyprotex in 1999, initially leading the company’s modelling efforts in PK prediction, over time extending the company’s capabilities into prediction of toxicity and pharmacological activity.

Watch the webinar to learn more!

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Tags: Videos & Webinars, ADME/DMPK, Modelling and Simulation

A Focus on Drug Transporters Webinar Series - Christine Bowman, Genentech

Posted by Evotec on Jan 26, 2022 5:11:55 PM

Investigating Protein-Facilitated Uptake of OATP Substrates: From In Vitro Data to PBPK Modeling

The fourth and final webinar in this series on drug transporters was presented by Christine Bowman from Genentech.

 


About the Webinar

 

Christine will discuss the concept of protein-facilitated uptake and the recently proposed hypothesis of a transporter-induced protein binding shift In vitro data generated with hepatocytes and HEK293 cells will be described as well as the results of using the HEK293 data for input in PBPK models. The results suggest that high affinity binding to transporters may change the equilibrium of nonspecific binding between drugs and plasma proteins, leading to greater cellular uptake and clearance than currently predicted.

 


About the Speaker

 

Christine Bowman

Christine Bowman PhD

Associate Scientist, DMPK | Genentech

Christine Bowman is an Associate Scientist in the Drug Metabolism and Pharmacokinetics Department at Genentech, Inc. Her research interests include improving in vitro to in vivo extrapolation with new in vitro methods and PBPK modeling. Prior to Genentech, Christine received her PhD from the University of California, San Francisco in the laboratory of Dr. Leslie Benet during which time she was the recipient of a National Science Foundation Graduate Research Fellowship and PhRMA Foundation Pre-Doctoral Fellowship in Pharmaceutics. Christine is an author and coauthor of 16 peer-reviewed scientific publications.

Watch the webinar to learn more!

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Tags: Videos & Webinars, ADME/DMPK

A Focus on Drug Transporters Webinar Series - Felix Huth, Novartis

Posted by Evotec on Jan 26, 2022 5:05:23 PM

Impact of Pre-incubation Time on Transporter Inhibition Potency

The third webinar in our series on drug transporters was presented by Felix Huth from Novartis.

 


About the Webinar

 

For some inhibitor compounds, pre-incubation with the inhibitor leads to more potent IC50 values in uptake transporter inhibition assays. One contributing factor to the higher inhibition potency is the time required to reach steady state concentrations for the inhibitor. The dependent factors influencing this equilibration time will be described as well as the clinical relevance.

 


About the Speaker

 

Felix Huth

Felix Huth PhD

ADME Scientist | Novartis

Felix Huth received his PhD in Natural Product Chemistry from the University of Göttingen, Germany. After starting his career in a Biotech company in 1999, he joined the pharmaceutical company Altana in 2004 as biotransformation specialist. He extended his ADME knowledge, i.e. in enzyme and transporter kinetics, PBPK modeling and DDI. After joining Novartis in 2013, he developed in the role of an ADME/DDI specialist with focus on transporters and PBPK modeling, reflected by more than 20 peer-reviewed publications.

Watch the webinar to learn more!

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Tags: Videos & Webinars, ADME/DMPK

A Focus on Drug Transporters Webinar Series - Birk Poller, Novartis

Posted by Evotec on Jan 26, 2022 4:42:54 PM

P-gp Transport Kinetics - Compound-Specific Selection of In Vitro Assay Design and Kinetic Parameter Estimation

The second webinar in this series on drug transporters was presented by Birk Poller from Novartis.

 


About the Webinar

 

Robust and reliable determination of the kinetic parameters for efflux transporters, primarily P-glycoprotein, has remained a challenging task. Different cell types, assay setups and kinetic models together with the physicochemical drug properties affect the outcome of in vitro studies. In this webinar, the results of a systematic study will be presented together with a compound-specific guidance for the assessment of efflux transporter kinetics.

 


About the Speaker

 

Birk Poller

Birk Poller
Senior Principal Scientist | Novartis

Birk Poller is an ADME Scientist at Novartis, working in the Pharmacokinetic Sciences department. He is responsible for in vitro permeability and drug transport studies and acts as deputy lead for an in vitro enzyme, transporter and plasma protein binding group. In addition, Birk Poller serves as ADME and DDI expert in cross-functional project teams throughout the translational drug development phases. His recent research on elucidating the interplay between drug transport and metabolism in the context of clearance prediction and drug-drug interactions resulted in several scientific publication. Before joining Novartis in 2010, Birk obtained his PhD from the University of Basel, Switzerland and he conducted postdoctoral research in blood-brain barrier pharmacokinetics at the Netherland Cancer Institute in Amsterdam.

Watch the webinar to learn more!

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Tags: Videos & Webinars, ADME/DMPK

A Focus on Drug Transporters Webinar Series - Hayley Atkinson, Cyprotex

Posted by Evotec on Jan 18, 2022 1:31:43 PM

Quantitative Prediction of Drug-Drug Interactions with Common Statin Co-meds: A Framework for Decision-making within Drug Discovery/Development

The first webinar in this series on drug transporters was presented by Hayley Atkinson from Cyprotex.

 


About the Webinar

 

Due to polypharmacy, drug-drug interactions (DDIs) continue to account for 5% of UK hospital admissions and as such remain a major regulatory concern. This is particularly true for common co-meds such as statins which due to their prescribing prevalence in patients with co-morbidities have high potential for DDI. Within Drug Discovery and Development we are moving away from relatively simple hazard identification of DDI potential using basic static equations detailed in regulatory guidance to actual risk analysis and mitigation using quantitative prediction of DDI. Using mechanistic static equations we can predict the AUC change of each statin due to inhibition of its critical enzyme/transporter pathway(s) so that the clinical team can make a decision on whether any potential DDI is simply a pharmacokinetic DDI or a clinically significant DDI requiring intervention. The statin mechanistic equation model requires very few in vitro input parameters and can be utilised towards aiding preclinical development candidate selection and towards reducing unexpected clinical findings in patients providing a useful tool in Drug Discovery and Early Development.

 


About the Speaker

 

Hayley Atkinson

Hayley Atkinson PhD
Associate Principal Scientist | Cyprotex

Hayley Atkinson is an Associate Principal Scientist in the permeability and drug transporter team at Cyprotex, UK where she acts as deputy scientific lead for drug transporter studies.  Her research interests include prediction of transporter mediated drug-drug interactions with improved in vitro assays.  Prior to joining Cyprotex in 2013, Hayley received her PhD from the University of Liverpool under Prof. Munir Pirmohamed where she conducted research on anti-epileptic drug transporters at the blood-brain barrier in the context of drug resistance.

Watch the webinar to learn more!

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Tags: Videos & Webinars, ADME/DMPK

Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors

Posted by Evotec on Sep 30, 2021 7:41:42 PM

Alastair Parkes, Ph.D, Group Leader, Discovery Chemistry, Evotec UK

As part of our ongoing efforts at Evotec to tackle AMR through the design of novel antibiotics we have been working with Boston-based X-Biotix in a collaboration focussed on targeting priority Gram-negative pathogens. We are now able to share the story of our work on inhibitors of UDP-N-Acetylglucosamine Acyltransferase (LpxA), a key enzyme in the biosynthetic pathway of the outer membrane lipopolysaccharide of Gram-negative bacteria. Building on hit-finding work at X-Biotix we put together a multi-disciplinary team including Medicinal Chemistry, Computational Chemistry, Structural Biology and DMPK at our Abingdon UK site, in vitro and in vivo Microbiology and PK at our Alderley Park UK site, and in vitro Biology at our site in Hamburg, Germany. Through structure and property-based optimisation we were able to design highly potent inhibitors of Pseudomonas aeruginosa LpxA that were active against multi-drug resistant clinical isolates. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa bacteria. In our paper in the Journal of Medicinal Chemistry we share the optimisation story, along with a significant quantity of activity data that we hope will be useful for other teams working on small molecule strategies to tackle P. aeruginosa and other Gram-negative bacteria.

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Tags: Antibacterial, Medicinal Chemistry, Articles & Whitepapers, ADME/DMPK, In vitro Biology, In vivo Pharmacology, Anti-Infectives, Antimicrobial resistance

Pharmacokinetic Prediction Fact Sheet

Posted by Evotec on Sep 9, 2021 5:52:45 PM

Learn more about human pharmacokinetic prediction including:

  • background information on the predictive model
  • in vitro ADME data and structural data requirements for PK prediction
  • data delivered for the PK prediction
  • validation data for the predictive model
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Tags: Fact Sheets, ADME/DMPK, Modelling and Simulation

Brain Tissue Binding Fact Sheet

Posted by Evotec on Sep 1, 2021 3:17:35 PM

Learn more about the brain tissue binding assay including:

  • Background information
  • Assay details and protocol summary
  • Data generated in the brain tissue binding assay
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Tags: Fact Sheets, ADME/DMPK